Methods
Twenty-six male athletes (track and field) under age 30 were enrolled. All were healthy and on no medication. None was overweight or obese (body-mass index <25 in all participants) and all had good echocardiographic windows.
The MM was performed in the left lateral decubitus position. A nose clip and mouthpiece were positioned before each manoeuver; the mouthpiece incorporated a small air leak (via 3-way stopcock) to prevent complete closure of the glottis at the time of inspiratory effort. During the manoeuver, mouth pressure was visually monitored by participants, who were trained to generate a target intrathoracic pressure of −40 mm Hg (−54.4 cm H2O, −5.333 kPa). After assuring that this goal was met, participants were coached in performing a series of five to six gasping efforts (as opposed to a sustained MM) over a period of 20±3 s. Separate runs were made for atrial size and Doppler flow recordings. Between each run participants rested a few minutes to allow baseline physiology to be re-established.
For measurement of atrial area, two-dimensional echocardiographic imaging was performed from the apical four-chamber view. Baseline recordings were acquired during quiet respiration (5–8 cardiac cycles). Twenty second loops were then recorded taking care to assure that both atria were optimally visualised throughout. Recording started a few beats before onset of the manoeuver and continued during performance of the series of gasping efforts. These were repeated as needed to obtain adequate echocardiographic images.
For Doppler flow recordings pulsed wave Doppler flow imaging across the mitral and (separately) tricuspid valves was performed with the sample volume positioned between the leaflet tips when the valve was fully open. As before, participants rested a few minutes between runs to allow baseline physiology to be re-established. We attempted to record pulsed Doppler measurements during actual performance of the MM, but in most participants it was not possible to assure proper positioning of the sample volume while participants were making respiratory efforts. We therefore focused our attention on recordings made at baseline (during quiet respiration) and immediately on release of the MM, extending out at least eight cardiac cycles postmanoeuver.
Using the real-time two-dimensional images at baseline and during the MM, area of the right and left atria were traced for each beat using electronic calipers; values were recorded in systole when the atrium is largest. We also recorded, at baseline and during the MM, whether the mitral or tricuspid valve was the first to open in diastole, or whether both valves opened simultaneously. Using the Doppler flow recordings, mitral and tricuspid valve E-wave and A-wave velocities were measured using electronic calipers, both at baseline and for each beat following completion of the MM.
All echocardiographic and Doppler measurements were made by a single reviewer blinded to the phase of the Mueller manoeuver.
This study was approved by the Institutional Review Board of the Albert Einstein Healthcare Network. All participants provided written informed consent.
Statistical analysis
The analysis of atrial area measurements proceeded as follows for the left atrium (LA) and right atrium (RA) separately. Each of the participants with atrial area measurements had the mean and variance of his baseline values calculated, and the mean and variance of his MM values calculated. Student's unpaired t test compared the grand average, using the pooled variance, at baseline to that during the MM, separately for the LA and RA, at a two-sided significance level of 0.05 without multiplicity correction. Fisher's F-test compared the variation in atrial area during the MM to that at baseline for each atrium separately using a 0.05 significance level.
The analysis of Doppler velocity measurements proceeded as follows, separately, for the E-wave and for the A-wave of each valve (mitral and tricuspid). For each of the 26 participants with velocity measurements, the average of his baseline values was compared in pairwise fashion to the value at his first cardiac cycle post-MM (pMM1) and separately, to that of his eighth cardiac cycle post-MM (pMM8). The pMM1 beat most closely represents that during the MM and the pMM8 beat represents short-term recovery from the MM. Paired Student's t test performed these comparisons at a two-sided significance level of 0.05 without multiplicity correction.